The present invention is concerned with a feline herpesvirus (FHV) mutant comprising a mutation in a section of the FHV genome, a nucleic acid sequence comprising said section of the FHV genome, a nucleic acid sequence comprising a heterologous DNA sequence flanked by DNA derived from said section, a recombinant DNA molecule comprising such nucleic acid sequences, a cell culture infected with an FHV mutant, as well as vaccine comprising the FHV mutant.
One of the major clinical problems in diseases of Felidae is associated with respiratory tract infections. The great majority of these cases are caused by either feline herpesvirus 1 (FHV) or feline calicivirus.
FHV is the causative agent of feline viral rhinotracheitis in cats. In kittens, FHV infection can generalize resulting in mortality rates of up to 50%. The disease is common and is found world-wide and is characterized by sneezing, depression, and ocular and nasal discharge.
The FHV is a member of the family Herpes-viridae, subfamily A,-herpesvirus. The genome is about 126 kb in length and is composed of a unique long (UL) region of about 99 kb and a short region of 27 kb comprising an unique short (Us) region of about 9 kb flanked by inverted repeats of about 8 kb (Grail et al., Arch. Virol. 116, 209-220, 1991).
Because of the prevalence and seriousness of FHV infection, feline viral rhinotracheitis vaccines comprising modified live or killed FHV have been developed and have resulted in a successful reduction of the incidence of the disease.
In addition to FHV infection, cats are also susceptible to infection by various other pathogens, such as feline leukemia virus, feline calicivirus, feline immunodeficiency virus, feline coronavirus and feline Chlamydia.
At present, in general, cats can be protected against infection by these pathogenic micro-organisms with live or inactivated vaccines.
However, these types of vaccines may suffer from a number of drawbacks. Using attenuated live vaccines always involves the risk of inoculating animals with inadequately attenuated pathogenic micro-organisms. In addition, the attenuated pathogens may revert to a virulent state resulting in disease of the inoculated animals and the possible spread of the pathogen to other animals.
Inactivated vaccines generally induce only a low level of immunity, requiring repeated immunizations. Furthermore, the neutralization inducing antigenic determinants of the pathogens may become altered by the inactivation treatment, decreasing the protective potency of the vaccine.
Moreover, a problem with combined live viral vaccines is the mutual influence of the antigenic components resulting in a decrease of the potency of one or more of the constituting components.
Furthermore, with currently administered live attenuated or inactivated FHV vaccines it is not possible to determine whether a specific animal is a carrier of an FHV field virus or whether the animal was vaccinated. Hence, it is important to discriminate between animals vaccinated with an FHV vaccine and those infected with a field virus so as to be able to take appropriate measures to reduce spreading of a virulent field virus. The introduction of for example a serologically identifiable marker can be achieved by introducing a mutation in genes encoding non-essential (glyco) proteins of the FHV which normally give rise to the production of antibodies in an infected host animal.
It is an object of the present invention to provide an FHV mutant which can be used not only for the preparation of a vaccine against feline viral rhinotracheitis but also against other infectious diseases of Felidae, which obviates any potential risk associated with the use of a live attenuated pathogen as a vaccine, which stimulates both the humoral and cellular immune system in a potent way without the explicit need of an adjuvant and which offers the possibility of a multivalent vaccine without the risk of adverse mutual interference of different antigenic components.
An other object of the present invention is to provide an FHV vaccine virus which is distinguishable from any field strain or any other FHV vaccine virus.